Scalp colonization by Trichophyton tonsurans in an urban pediatric clinic. ?Asymptomatic carrier state.

Random culturing of the scalp in 200 healthy children in a large metropolitan children's hospital revealed that eight (4%) of the patients had cultures that were positive for Trichophyton tonsurans variety sulfureum. Infections were not clinically apparent and were asymptomatic. All of the patients with positive cultures were black and six braided their hair. Trichophyton tonsurans appears to exist in an asymptomatic state in this well-defined population of children.

Diagnostic procedures of the skin. Part one: Wood's light, KOH slide, Gram's stain, and cultures.

The diagnosis of skin lesions involves the same priniciples and methodology required in other medical problems. Visual recognition alone and "shotgun" therapy is not a satisfactory clinical approach. A disciplined and careful examination of lesions, establishment of a differential diagnosis, and selection of appropriate procedures are frequently necessary for cutaneous diseases. The indications, limitations, interpretation, and techniques of diagnostic procedures must be well understoood to obtain reliable information. Not all tinea capitis will reveal fluorescence with Wood's light examination, but the Wood's light may be particularly helpful in the diagnosis of tinea versicolor, erythrasma, porphyria, and tuberous sclerosis. Bacterial growth on cultures taken from the skin does not necessarily mean infection. Because the eczematous skin teems with bacteria, there must be a careful interpretation of the cultures results within the context of the clinical situation. This paper is the first in a two-part series dealing with selected cutaneous procedures which are useful to the family physician in everyday practice.

Diagnostic procedures of the skin. Part two: Skin biopsy and other tests.

The diagnosis of skin lesions involves the same principles and approaches required for other clinical problems. "Shotgun" therapy based on visual recognition alone is not an adequate clinical approach. A pertinent history and careful physical examination, supplemented by carefully selected diagnostic procedures, is usually necessary for skin diseases. The indications, limitations, interpretation, and techniques of diagnostic procedures must be well understood to obtain reliable and useful information. The selection of the specific method of skin biopsy, for example, may be based on cosmetic considerations, location and nature of the lesion, and the physician's understanding of the biology and histopathology of the suspected diagnosis. This is the second paper in a two-part series dealing with diagnostic procedures of the skin. Various kinds of skin biopsy, touch imprints, the Tzanck smear, and immunofluorescent studies are described as they relate to the everyday practice of the family physician.

Evaluation of the adult carrier state in juvenile tinea capitis caused by Trichophyton tonsurans.

The anthropophilic dermatophyte Trichophyton tonsurans is an occasional cause of scalp ringworm in adults. An asymptomatic adult carrier state also has been described. In this study the parents and/or grandparents of 50 children with proved T. tonsurans tinea capitis were evaluated. Cultures were obtained from the scalps of 46 asymptomatic adults; 14 of the cultures grew T. tonsurans. This population may provide a source for continued reinfection in children.

Tinea nigra masquerading as acral lentiginous melanoma.

Tinea nigra is a superficial mycosis that may mimic serious pigmentary lesions. A lesion recently encountered on the foot was suspected of being a malignant melanoma. Histologic and mycologic studies, done after a biopsy was obtained, demonstrated Exophilia werneckii in the stratum corneum. Tinea nigra should be considered in the diagnosis of pigmented lesions of the hands and feet. A KOH examination is a simple and rapid means of demonstrating this entity.

Dermatophytosis of the scalp: incidence, immune response, and epidemiology.

Tinea capitis remains a common infection among the pediatric population of North America. The 'gray patch' Microsporum audouinii infections of the 1950's have been supplanted by the 'black dot' ringworm of Trichophyton tonsurans. The clinical presentation of T. tonsurans infection is quite variable and may be related to specific host T-lymphocyte response. This dermatophytosis is most frequently incurred from contact with an infected child either directly or via a variety of fomites. Current studies indicate that an asymptomatic adult carrier state may also exist which could contribute to the morbidity of this mycosis.

Studies on human porin. VI. Production and characterization of eight monoclonal mouse antibodies against the human VDAC "Porin 31HL" and their application for histotopological studies in human skeletal muscle.

We report on the production and characterization of eight monoclonal mouse antibodies against the complete human VDAC "Porin 31HL". The antigen used was purified from a total membrane preparation of the transformed human B-lymphocyte cell line H2LCL. In Western blots all eight mAbs react with a single 31-kDa band in solubilized H2LCL membrane preparations thus demonstrating their specificity for the human VDAC "Porin 31HL". Concerning the epitope specificity we show that all eight mAbs equally react with the N-terminal part of human porin. Moreover, we demonstrate the expression of VDAC in the sarcolemma by indirect immunoenzyme labelling of cryosections of human skeletal muscle applying four of our mAbs. These data support our recent observations on the expression of porin channels in the plasmalemma of different normal and transformed human cell lines. VDAC in the plasmalemma is discussed as the molecular basis of the Blatz and Magleby channel.

[Studies on human porin. V. The expression of "porin31HL" in the plasmalemma is not by cell transformation]. / Zur Kenntnis der Porine des Menschen. V. Die Plasmalemmständigkeit von "Porin 31HL" ist keine Folge einer Zell-Transformation.

In recent papers we proved "Porin 31HL" to be located on the surface of human, EBV-transformed B lymphocytes. Here we present proof of "Porin 31HL" in the plasmalemma of normal human blood lymphocytes. For this purpose B and T lymphocytes were isolated from human heparinized blood and examined by indirect immunofluorescence techniques using different monoclonal antibodies against purified "Porin 31HL" and some B and T cell markers, respectively. For comparison a number of established cell lines of different origin were employed. Hence it followed that normal B and T cells as well as transformed and leukemic cells express "Porin 31HL" in their membrane. No significant quantitative differences could be seen. Consequently, the location of "Porin 31HL" in the plasmalemma is not a product of transformation.

[A flip-flop model of the chloride channel complex explains the dysregulation of the chloride flow in the plasmalemma of cells in cystic fibrosis]. / Ein Flip-Flop-Modell des Chlorid-Kanal-Komplexes erklärt die Fehlregulation des Chloridflusses am Plasmalemm von Zellen bei der cystischen Fibrose.

The basic defect in cystic fibrosis is the chloride impermeability of the plasmalemma in different cells. A candidate for the chloride channel, thought to be affected in the syndrome, is "Porin 31HL" recently described by us. The molecule is i) expressed in the plasmalemma of different cells, it has ii) a molecular mass of 31,000 Daltons, it shows iii) high conductance in artificial membranes and it can be iv) modified by 4,4'-Diisothiocyanatostilbene-2,2'-disulfonate. A porin in the outer membrane of cells should furthermore v) be regulated by modulators. All these characters of "Porin 31HL" correspond to those given in literature for chloride channels. The regulation of the channels can be explained by a two component flip flop model.

Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a potent antifungal agent related to the allylamines, has been used in Japan for treating various cutaneous mycoses including tinea cruris. OBJECTIVE: We compared the safety and efficacy of butenafine hydrochloride and its vehicle when used once daily for 2 weeks to treat tinea cruris. METHODS: Patients (n = 93) with tinea cruris and a positive potassium hydroxide examination and mycologic culture were enrolled. Of the 76 patients assessed for efficacy, 37 applied butenafine and 39 applied vehicle once daily for 2 weeks. Assessments were made at the end of the 2-week treatment period and 4 weeks after the end of treatment. RESULTS: Patients in the butenafine group had a higher mycologic cure rate by day 7 (66% vs 13%, p < 0.0001), with marked improvement 4 weeks after the end of treatment (81% vs 13%, p < 0.0001). They also had a higher rate of effective treatment at day 7 (29% vs 5%, p < 0.01) and at 4 weeks after treatment (73% vs 5%, p < 0.0001). Adverse events definitely related to butenafine treatment were limited to one case of burning sensation after application. CONCLUSION: Butenafine applied once daily for 2 weeks is effective in treating tinea cruris. The proportion of patients cured increased between the end of treatment and 4 weeks after treatment.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. RESULTS: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. CONCLUSION: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail.

BACKGROUND: Fluconazole is a bis-triazole antifungal agent approved for the treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic candidal infections, and cryptococcal meningitis. OBJECTIVE: The purpose of this study was to evaluate three different durations of once-weekly fluconazole for the treatment of onychomycosis of the toenail caused by dermatophytes. METHODS: In a multicenter, randomized, double-blind, parallel, placebo-controlled trial, 384 patients with distal subungual onychomycosis of the toenail received fluconazole, 450 mg once weekly, or placebo for 4, 6, or 9 months. For inclusion, patients were required to have mycologically confirmed distal subungual onychomycosis of the toenail with a large toenail at least 25% clinically affected but having at least 2 mm of healthy nail between the nail fold and the proximal onychomycotic border. Efficacy was assessed by clinical and mycologic (microscopic and microbiologic) measures at screening, at every treatment visit starting at month 3, and at months 2, 4, and 6 after therapy. Observed or volunteered adverse events were recorded and classified at all visits. RESULTS: At the end of treatment, very significantly superior clinical and mycologic results were achieved in all fluconazole groups compared with placebo (p=0.0001). This superiority was largely maintained over 6 months of follow-up. The clinical and mycologic responses of the 9-month treatment duration were significantly superior to the 4- and 6-month durations. Similar percentages of patients in the fluconazole and placebo groups reported adverse experiences for all three durations of the study. CONCLUSION: Results of this study support the efficacy and safety of fluconazole in the treatment of distal subungual onychomycosis of the toenail.

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.